Genetic mutations in the REST gene have been shown to cause Wilms tumor, a rare kidney cancer that occurs in children. The findings, published in Nature Genetics (doi:10.1038/ng.34400), identified mutations in the REST gene in 16 children with Wilms tumor.

Wilms tumor affects approximately 1 in 10 000 children, but fortunately is curable in an estimated 90% of them.

Nine of the 16 children in the study were the only members of the family to develop Wilms tumor, but in 4 families more than 1 child had developed the cancer. It was the clustering of cases of this rare cancer that alerted the researchers that a hereditary genetic cause was likely. They estimate that REST mutations cause approximately 10% of familial Wilms tumor.

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The study, led by researchers at The Institute of Cancer Research, London, United Kingdom, is part of the Factors Associated with Childhood Tumours (FACT) study. The FACT study is uncovering genetic causes of childhood cancers and has participants from more than 5 000 families. The FACT study is funded by the Wellcome Trust and the Rosetrees Trust, and the REST project involved international collaborators including from Baylor College of Medicine in Houston, Texas.

REST is a well-studied gene because of its critical role in embryo development, but this research brings a new, previously unrecognized, role of REST to the field of human genetics.

The mutations found in children with Wilms tumor appear to compromise the normal functioning of REST in regulating the development of the embryo.

“We hope our findings will stimulate research into why and how these REST mutations, which all cluster in a particular part of the gene, cause cancer,” said study leader Professor Nazneen Rahman, PhD, head of Genetics and Epidemiology at The Institute of Cancer Research, London, and head of Cancer Genetics at The Royal Marsden NHS Foundation Trust.

“Our findings are also of immediate value to families, who now have an explanation for why their child got cancer. Moreover, we can now do a simple blood test to see which children in the family are at risk of cancer and may benefit from cancer screening, and which have not inherited the mutation and so are not at increased risk of cancer. This kind of information is really valuable for the families of children with cancer.”